Farr B M, Gwaltney J M
J Chronic Dis. 1987;40(9):875-9. doi: 10.1016/0021-9681(87)90187-1.
A recently published randomized, controlled, double-blind, study has reported efficacy of zinc gluconate lozenge treatment of the common cold. Because of a higher rate of side effects in the zinc group and the lack of any confirmatory evidence of blinding efficacy, we are concerned about the possible contribution of bias to the study result. Unflavored zinc gluconate tablets can be easily distinguished from the relatively tasteless, unflavored calcium lactate tablets, which were used as placebo in the cited study, increasing our concern about bias. In order to be able to test zinc lozenges in a second trial of common cold therapy, we developed a matching placebo containing denatonium benzoate (a bitter substance used to prevent thumb sucking in children) and then undertook a formal evaluation of blinding efficacy. This article reports the results of this evaluation, encompassing two randomized, controlled taste trials; the first trial of the placebo matching showed zinc recipients to exhibit a higher rate of side effects and also a significantly higher proportion of subjects believing they were on "active" treatment. Alterations in dosage before the second taste trial yielded comparability of the placebo and zinc lozenges. This study illustrates the pitfalls which may sometimes be encountered in performing and publishing studies in which placebos are either not tested at all or tested in too small a subject population to detect a significant subjective difference between the placebo and the active medication.
最近发表的一项随机、对照、双盲研究报告了葡萄糖酸锌含片治疗普通感冒的疗效。由于锌组副作用发生率较高，且缺乏任何关于盲法有效性的确证证据，我们担心偏倚可能对研究结果产生影响。无味的葡萄糖酸锌片很容易与相对无味的乳酸钙片区分开来，而乳酸钙片在上述研究中用作安慰剂，这增加了我们对偏倚的担忧。为了能够在普通感冒治疗的第二项试验中测试锌含片，我们研制了一种含有苯甲地那铵（一种用于防止儿童吮拇指的苦味物质）的匹配安慰剂，然后对盲法有效性进行了正式评估。本文报告了这项评估的结果，包括两项随机对照味觉试验；安慰剂匹配的第一项试验显示，服用锌的受试者副作用发生率较高，而且认为自己接受“活性”治疗的受试者比例也显著更高。在第二项味觉试验前调整剂量后，安慰剂和锌含片具有可比性。这项研究说明了在进行和发表研究时可能遇到的陷阱，即要么根本不测试安慰剂，要么在太小的受试者群体中进行测试，以至于无法检测到安慰剂与活性药物之间的显著主观差异。
